The present study provides evidence that the chronic activation of TRPV1-positive afferent renal nerves by OLDA has a neuroprotective effect on HFD-induced impairment in TRPV1-positive afferent renal nerves, suggesting that TRPV1-positive afferent renal nerves might play a preventive role in the development of renal dysfunction and hypertension induced by obesity. Here, TRPV1 is linked to obesity due to melanocortin 4 receptor deficiency.